This invention relates generally to microcentrifugation instruments and techniques, specifically to an improved arrayable microcentrifuge for simultaneous centrifugation of samples.
Centrifugation as a means of accelerating sedimentation of precipitates and particulates has long been an integral part of biochemical protocols. A typical centrifuge consists of a rotor encased in a housing. The rotor is powered by a drive motor or some other force that allows it to complete a set number of rotations per minute (rpm). Attached to the rotor are holders in which to place sample containers, such as test tubes or well plates. These holders are placed symmetrically around the circumference of the rotor. The sample containers are balanced to insure a symmetric mass distribution around the rotor. The sample containers are placed in the holders and the samples can then be spun and separated.
Separation of the samples occurs because each component has a different density and thus a different sedimentation velocity. Sedimentation velocity is a measure of how fast a component will migrate through other more buoyant sample components as a result of the centrifugal field generated by the centrifuge.
Using centrifugation, a variety of samples can be separated. Specific types of cell organelles can be isolated, particles can be removed from a suspension, and different liquids in a solution can be separated. The amount of separation of a sample is determined by the rpm used and the length of time the sample is spun. Recently, the increasing demand for high-throughput assays in the field of biochemistry has created a need for parallel processing and automation of many such protocols. Standard centrifuges have proven to be incompatible with these needs.
The need for highly parallel sample processing has led the science community to usage of multiwell plates. Because of the plates"" insufficient mechanical strength, centrifugation of samples held in such plates is limited to accelerations below 3,500xc3x97g. Furthermore, multiwell plate centrifuges are large and cumbersome to automate. Though automation of centrifuge-based sample preparation has been performed (AutoGen 740, AutoGen, Framingham, Mass.), the resulting instruments have limits ( less than 96 samples/hr per instrument) as a result of these difficulties.
Filter-based separation protocols also have been automated by several companies (Qiagen, Chatsworth, Calif., and Beckman Coulter, Palo Alto, Calif) but also are limited in throughput (roughly 96 samples/hr per instrument) and are at least 10 times more expensive than centrifuge-based separations.
The main limitations of centrifuges are 1) the need for a large amount of manual labor to load and unload them, 2) the small number of samples that can be spun down at one time, and 3) the length of time it takes to spin down samples. In addition, the maximum acceleration used in current centrifuges is limited by the mechanical strength of the sample containers, particularly multi-well plates, which increases the amount of time needed to spin down samples. Although these problems could be overcome by the use of robotic arms and the purchase of more centrifuges, the cost and space requirements would be prohibitive for most laboratories.
PCT Application No. PCT/US98/18930 (published as International Publication No. WO 99/12651) addresses some of these problems by disclosing a high-throughput centrifugation system in which samples are spun directly in contact with individual, miniature rotors rather than a sample holder. However, this system does not disclose an efficient means for the simultaneous rotation and restraint of the rotors. Moreover, this application does not disclose an efficient means for containing samples and protecting the apparatus from spillage. What is needed is a reliable and efficient high-throughput automated centrifugation apparatus.
In one embodiment, a microcentrifuge apparatus has a plurality of rotors for simultaneously spinning a plurality of samples; a retainer for retaining each of the rotors on a bearing surface; and at least one source of motive power (i.e., a motor), coupled to the rotors by a coupling means, for causing each of the rotors to spin at substantially the same rate. The coupling means is preferably a drive belt such as a single continuous drive belt.
In another embodiment, the microcentrifuge apparatus has a plurality of rotors for spinning a plurality of samples; a retainer for retaining each of the rotors on a bearing surface; at least one source of motive power for spinning the rotors; and at least one drive belt, coupled between the power source and each of the rotors, for applying the motive power to each of the rotors.
In another embodiment, the microcentrifuge has a plurality of rotors, each having a longitudinal axis and each containing a sample, a plurality of retainers for retaining each rotor at its predetermined location; a bearing surface located at each predetermined location for supporting each rotor as it is spun; and a source of rotating power coupled to the rotors for spinning each rotor on its longitudinal axis.
In another embodiment, the micro-array centrifuge has the following: a. a lower plate with a plurality of recesses; b. an upper plate with a plurality of holes, each hole lined by a raised cuff; c. a plurality of rotors, each having a longitudinal axis, top, bottom, crown, side and upper shaft, the side and crown maintaining contact with a drive belt; d. a motor for moving the drive belt, which in turn spins the rotors about their longitudinal axes; e. a cap with an inner and an outer lip, the inner lip adhering to the upper shaft and the outer lip being outside of the raised cuff and in close proximity to the top surface of the top plate, whereby fluid is prevented from getting into the microarray centrifuge; and f. each rotor bottom contacting at least one bearing which contacts at least one recess in the lower plate.
In another embodiment, the microcentrifuge has a lower plate divided into strips, each of which is anchored at its end.
In another embodiment, the microcentrifuge has a plurality of disposable rotors for simultaneously spinning a plurality of samples, a retainer for retaining each of the rotors on a bearing surface; and a source of motive power, coupled to the rotors, for spinning each of the rotors at substantially the same rate. The disposable rotors fit into and are removable Prom a plurality of rotor encasements of the array centrifuge. The disposable rotors comprise one or more chambers for samples.